ProMIS uses its proprietary discovery engine, consisting of two complementary algorithms, ProMIS™ and Collective Coordinates, to identify specific targets on misfolded proteins that are known root causes of neurodegenerative diseases. Such misfolded proteins are directly toxic to neurons and spread (propagate) in the brain or spinal cord, killing billions more neurons and leading to neurodegenerative diseases.
ProMIS has developed a rigorous screening and validation process to select the best in class product candidates to develop among our emerging portfolio of precision therapeutics. The process starts with identification of specific targets (epitopes) on the prion forms of misfolded proteins. Murine monoclonal antibodies (mAbs) are raised against these targets and evaluated in a 3-step process, to identify the best products to take into clinical development.
Initial Screening for Binding. This phase allows to identify mAbs that bind uniquely and specifically to the prion strains of the misfolded proteins driving Alzheimer’s disease (Amyloid beta oligomers, or AβO, and Tau), Amyotrophic lateral sclerosis or ALS (SOD1 and TDP43 proteins) and Parkinson’s disease (alpha synuclein). The top candidate products, showing selective binding to the toxic, prion-like forms and no binding to the non-toxic forms of the relevant protein, are selected for the validation phase in human tissue.
Functional Assays & final product candidate selection. Two complementary assays are used to identify, among the validated product candidates, those that demonstrate blocking of neurotoxicity (blocking the killing of neurons, a hallmark of disease) and inhibition of propagation (spreading throughout the brain) of the prion-like strains of misfolded protein (also a hallmark of disease). Validated product candidates meeting these criteria undergo final testing to confirm that they block neurotoxicity in an acute animal model.
For Alzheimer’s disease, our most advanced priority program, three validated product candidates have been designated: PMN310, PMN350, and PMN330.